Hairy cell leukemia: a ‘hair-raising’ update

Abstract

Hairy cell leukemia (HCL) is an uncommon low grade B cell leukemia that is marked by pancytopenia, splenomegaly, and characteristic cytoplasmic hairy projections. The current standard of care is treatment with purine analogs, like cladribine or pentostatin, which provide a high complete remission rate with a median duration of response of 5 years. Many patients who show initial remission will relapse, and others with refractory disease may show no response. The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib. Targeted immunotoxins remain an interesting area of study. The use of the monoclonal antibody rituximab in combination with purine analogs appears to produce even higher responses, often employed to minimize or eliminate residual disease. With our current understanding of B cell signaling pathways, the development of kinase inhibitors appears promising and may change the future therapeutic landscape of this rare disease.

Keywords::

• chemotherapeutics
• cladribine
• hairy cell leukemia
• immunotoxins
• pentostatin
• relapsed hairy cell leukemia
• variant hairy cell leukemia
• vemurafenib

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hairy cell leukemia (HCL) is an indolent lymphoproliferative disorder characterized by pancytopenia, splenomegaly and ‘hairy’ cytoplasmic projections.

• Standard of care treatment in a newly diagnosed patient is with the purine analogs cladribine or pentostatin, attaining response rate in excess of 80–90%.

• The discovery that the majority of patients with classical HCL have a mutated V600E mutation has led to studies evaluating BRAF inhibitors like vemurafenib.

• In patients who have a short remission or those with refractory disease, multiple options are available including single-agent rituximab, the addition of rituximab to a purine analog or treatment via various clinical trials utilizing vemurafenib, bendamustine, ibrutinib and the targeted immunotoxins.

Notes